Abstract
The identification of common targets in Alzheimer’s disease (AD) and cardiovascular disease (CVD) in recent years makes the study of the CVD/AD axis a research topic of great interest. Besides aging, other links between CVD and AD have been described, suggesting the existence of common molecular mechanisms. Our study aimed to identify common targets in the CVD/AD axis. For this purpose, genomic data from calcified and healthy femoral artery samples were used to identify differentially expressed genes (DEGs), which were used to generate a protein–protein interaction network, where a module related to AD was identified. This module was enriched with the functionally closest proteins and analyzed using different centrality algorithms to determine the main targets in the CVD/AD axis. Validation was performed by proteomic and data mining analyses. The proteins identified with an important role in both pathologies were apolipoprotein E and haptoglobin as DEGs, with a fold change about +2 and −2, in calcified femoral artery vs healthy artery, respectively, and clusterin and alpha-2-macroglobulin as close interactors that matched in our proteomic analysis. However, further studies are needed to elucidate the specific role of these proteins, and to evaluate its function as biomarkers or therapeutic targets.
Highlights
IntroductionCardiovascular disease (CVD) is the leading cause of mortality worldwide
Large low-density lipoprotein (LDL) particles have been found to correlate significantly study we found strong evidence in the scientific literature that could link this target to the cardiovascular disease (CVD)/Alzheimer’s disease (AD) axis
Our study identified some potential novel targets in the CVD/AD axis, including apolipoprotein E (APOE), HP, CLU and A2M, being the two first proteins up- and downregulated, respectively, in atherosclerotic vascular tissue compared with healthy vascular tissue
Summary
Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Health Organization (WHO) estimates that in 2015 (the latest year for which data have been published), 31% of all deaths worldwide were due to CVD. CVD is mainly caused by the development of atherosclerosis, and encompasses coronary heart disease, peripheral arterial disease and cerebrovascular disease. There are several well-known risk factors that increase the likelihood of developing CVD, such as hypertension, smoking, decreased serum high-density-lipoprotein (HDL), increased serum low-density lipoprotein (LDL), diabetes, sedentary lifestyle, obesity, family history, age, and alcohol consumption. Scientific evidence has shown that CVD could be related to other pathologies which a priori might
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